The roles of inflammatory signals in cardiovascular remodeling
Project/Area Number |
16K09493
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Research Field |
Cardiovascular medicine
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Research Institution | The University of Tokyo |
Principal Investigator |
Takeda Norihiko 東京大学, 医学部附属病院, 特任講師 (40422307)
|
Project Period (FY) |
2016-04-01 – 2019-03-31
|
Project Status |
Completed (Fiscal Year 2018)
|
Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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Keywords | 心血管リモデリング / 線維化 / 炎症 / 心臓 / 血管 / リモデリング / 心臓リモデリング / 内科学 |
Outline of Final Research Achievements |
In this study, we evaluated the roles of inflammatory processes in cardiovascular remodeling. Using murine model of pressure-overload induced cardiac hypertrophy and fibrosis, we examined the roles of inflammatory macrophages during cardiac remodeling. We also established a murine model of pulmonary artery overflow vasculopathy, where we induced a volume shift of the pulmonary artery leading to the vascular remodeling. Based on the current model, we found that monocyte/ macrophages accumulate to the lung of overflow vasculopathy. We further examined the ischemic environment in fibroblasts activation. Through the genetic or pharmacological approaches, we found that hypoxia inducible factor mediated glycolytic reprograming elicits fibroblast activation. We also identified that serum starved environment accelerate collagen production in in vitro cultured fibroblasts. These results illuminate previously unidentified pathological processes which underlie cardiovascular remodeling.
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Academic Significance and Societal Importance of the Research Achievements |
高血圧症など生活習慣病では心臓、血管に障害が引きおこされ、心不全などの原因になります。これまで血圧変動などがどのように心血管病を発症させるのか、その病態は十分には分かっていませんでした。本研究では炎症プロセスに着目し、それらが心臓、血管病の発症にどのように関与するかを解析しました。今回の知見をもとに、心血管病に対する新たな治療法を開発する礎となる可能性が期待できると考えています。
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Report
(4 results)
Research Products
(6 results)
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[Journal Article] Cell cycle perturbation induces collagen production in fibroblasts.2019
Author(s)
Wake Masaki, Takeda Norihiko, Isagawa Takayuki, Sato Tatsuyuki, Nakagama Yu, Morioka Masaki, Hirota Yasushi, Asagiri Masataka, Maemura Koji, Manabe Ichiro, Tanabe Kazuaki and Komuro Issei.
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Journal Title
International Heart Journal
Volume: 印刷中
NAID
Related Report
Peer Reviewed / Open Access
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[Journal Article] Targeting HIF-1α/PDK1 Axis by Dichloroacetate (DCA) Suppresses Bleomycin-induced Pulmonary Fibrosis2018
Author(s)
Goodwin J, Choi H, Hsieh MH, Nuegent ML, Ahn JM, Hayenga HN, Singh PK, Shackelford DB, Lee IK, Shulaev V, Dhar S, Takeda N, Kim JW.
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Journal Title
Am J Respir Cell Mol Biol
Volume: 58
Issue: 2
Pages: 216-231
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research